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ID PMID Title PublicationDate abstract
17432853 Reaction of cytochrome P450BM3 and peroxynitrite yields nitrosyl complex. 2007 May 9 Peroxynitrite has come into the spotlight in recent years. Its effects on proteins have been implicated in several diseases such as acute lung injury, rheumatoid arthritis, implant rejection, artherosclerosis, Parkinson's disease, and Alzheimer's disease. Peroxynitrite is thought to inactivate a variety of proteins including thiolate-ligated heme proteins such as cytochrome P450 2B1 and PGI2 synthase, through the nitration of tyrosine residues. In previous studies it was reported that thiolate-ligated heme enzymes react with peroxynitrite to form a ferryl intermediate. In an effort to spectroscopically characterize this species in P450BM3, we discovered that the peroxynitrite-generated intermediate is not an FeIVoxo, but rather an iron-nitrosyl [FeNO]6 complex. We present density functional calculations as well as Mössbauer and stopped-flow spectroscopic characterizations of the peroxynitrite-generated intermediate in P450BM3.
17197238 The pathogenic role of tissue-resident immune cells in psoriasis. 2007 Feb Psoriasis is a common chronic inflammatory skin disease, the study of which might also be of considerable value to the understanding of other inflammatory and autoimmune-type diseases, such as rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis and diabetes mellitus. There is clear evidence that T cells and dendritic cells have a central role in psoriasis. Based on recent data from humans and animal models, we propose that a psoriasis lesion can be triggered and sustained by the local network of skin-resident immune cells. This concept focuses attention on local, rather than systemic, components of the immune system for rationalized therapeutic approaches of psoriasis and possibly also other chronic inflammatory diseases.
17083522 The feasibility of total ankle prosthesis for severe arthropathy in haemophilia and prothr 2006 Nov The standard treatment for end-stage arthropathy of the ankle joint in haemophilia has been fusion of the ankle joint. Total ankle replacement is used in osteoarthritis and especially in rheumatoid arthritis with good medium-term results. In this case series three patients are being described, in which a total of five total ankle replacements have been preformed. After a median follow up of 4.3 years (range 1-8.7) all prostheses were still in place and did not show any signs of loosening. Clinical scores showed a good to excellent result. In this small series total ankle replacement in patients with bleeding disorders show promising results. Further studies are needed to show the value of this relatively new type of surgery in haemophilic patients.
16813847 Emotion with tears decreases allergic responses to latex in atopic eczema patients with la 2006 Jul OBJECTIVE: Allergic responses are enhanced by stress, whereas they are reduced by laughter in atopic eczema patients. Emotion with tears decreases plasma IL-6 levels in patients with rheumatoid arthritis. Thus, the effect of emotion with tears on allergic responses in patients with atopic eczema was studied. METHODS: Sixty patients with atopic eczema having latex allergy viewed both the weather information video and the heart-warming movie, Kramer vs. Kramer. Just before and immediately after viewing each video, allergic responses to latex were measured. RESULTS: Viewing the weather information video did not cause emotion with tears in any patients, and it failed to modulate allergic responses. In contrast, viewing Kramer vs. Kramer caused emotion with tears in 44 of 60 patients, and it reduced allergic skin wheal responses to latex and latex-specific IgE production in them. CONCLUSION: Emotion with tears reduced allergic responses, and it may be useful in the treatment of allergic diseases.
16730216 Citrullination: a posttranslational modification in health and disease. 2006 Posttranslational modifications are chemical changes to proteins that take place after synthesis. One such modification, peptidylarginine to peptidylcitrulline conversion, catalysed by peptidylarginine deiminases, has recently received significant interest in biomedicine. Introduction of citrulline dramatically changes the structure and function of proteins. It has been implicated in several physiological and pathological processes. Physiological processes include epithelial terminal differentiation, gene expression regulation, and apoptosis. Rheumatoid arthritis, multiple sclerosis, and Alzheimer's disease are examples of human diseases where protein citrullination involvement has been demonstrated. In this review, we discuss our current understanding on the importance of protein deimination in these processes. We describe the enzymes catalyzing the reaction, as well as their known protein substrates. We review the citrullinated peptide epitopes that are proposed as disease markers, specifically recognized in certain human autoimmune disorders. The potential autopathogenic role of citrullinated epitopes is also discussed.
16624661 Rare association of chronic lymphocytic thyroiditis with dermatomyositis. 2006 May Autoimmune thyroid disease (AITD) has been associated with other autoimmune diseases such as chronic urticaria, insulin-dependent diabetes mellitus, Sjøgren's syndrome, inflammatory bowel disease, rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, psoriasis, ankylosing spondylitis, and dermatomyositis (DM). AITD is a common disorder affecting primarily women, and both genetic and environmental factors are included in its pathogenesis. DM is considered an autoimmune disease of the muscles and skin. Although AITD is the most common cause of hypothyroidism, to the best of our knowledge, only three cases of DM and AITD in the same patient have been reported in the last 40 years. We consider that both are developed from the same autoimmune background. Herein, we present a case of a 30-year-old man with a 4-year history of AITD who was diagnosed as suffering as well from DM.
16378005 Developments in the apheresis procedure for the treatment of inflammatory bowel disease. 2006 Jan Initially used to treat rheumatoid arthritis, nonselective therapeutic leukocytapheresis was applied to the treatment of inflammatory bowel disease (IBD) as early as the 1980s. Since then, the process has been further refined and 2 blood perfusion systems using membrane filtration are presently employed in Japan and Europe for the selective removal of leukocytes in patients with IBD: Cellsorba is a column of polyethylenephtarate fibers that captures lymphocytes and granulocytes, and Adacolumn is a column of cellulose acetate beads that selectively adsorb granulocytes and monocytes. These systems overcome the limitations of centrifugation. Leukocytapheresis has been shown to exert an overall anti-inflammatory effect, as peripheral leukocytes demonstrated a diminished capacity to produce inflammatory cytokines such as tumor necrosis factor-alpha, interleukin (IL)-1, IL-6, IL-8, and IL-1beta. In addition, down-regulation in the expression of adhesion molecule L-selectin and a shift toward a more immature granulocyte phenotype were observed in the peripheral blood. The safety and beneficial therapeutic effect of leukocytapheresis in IBD are being investigated further.
16193344 [Arthrodesis of the talonavicular joint]. 2006 Apr The talonavicular joint as part of the coxa pedis plays a pivotal role in the overall motion of the foot. The necessity for talonavicular fusion arises from isolated arthritis of posttraumatic, rheumatoid, degenerative, or idiopathic etiology. Posttraumatic arthritis is seen after malunited mid-tarsal (Chopart) fracture-dislocations and is frequently accompanied by malalignment due to an imbalance between the medial and lateral columns of the foot. In these cases a corrective arthrodesis becomes necessary. In cases of poor bone stock or arthritis of the calcaneocuboid joint, a double arthrodesis is preferred over isolated talonavicular fusion. Fusion with mini-plates is biomechanically superior to fusion with screws and especially staples, the latter being associated with non-union rates of up to 37%. Talonavicular fusion allows reproducible pain reduction in isolated arthritis with subjective patient satisfaction of between 86% and 100% in a literature review. The substantial reduction of movement in the triple joint complex leads to overload of the adjacent joints with development of arthritis in about 30% in the medium term.
18848698 The role of interferon gamma in regulation of CD4+ T-cells and its clinical implications. 2009 Interferon gamma (IFNgamma) plays a central role in the immune response against infection and tumur immune surveillance. Its functions include not only activation of the host immune system to control microbial infections but also repression of autoimmune responses by turning on T-regulatory cells and increasing T effector cell apoptosis. Defects in IFNgamma and IFNgamma receptor genes have been associated with autoimmune diseases such as rheumatoid arthritis, type 1 diabetes and multiple sclerosis. However, treatment of autoimmune diseases by supplementing with IFNgamma has been satisfactory due to its broad biological effects. Instead, its target T-regulatory cells may be used for the clinical treatment of autoimmune diseases. Future study could also focus on promotion of the beneficial effects of IFNgamma and blocking those unwanted IFNgamma-induced activities.
18692018 Identifying and characterizing the biological targets of metallotherapeutics: Two approach 2008 Nov 1 A significant challenge in the field of medicinal inorganic chemistry is the identification of biological targets of metal-based drugs and the characterization of the metal-biomolecule adducts. A classic example is Au(I), which has long been used to treat rheumatoid arthritis despite a poor understanding of its biological targets due to the lability, reactivity, and "spectroscopic silence" that are characteristic of Au(I). Here, we report two qualitative methods for characterizing Au(I)-protein adducts: a thiol-reactive probe that facilitates the identification of biological cysteine-Au(I) adducts and a photoreactive Au(I) complex that produces a covalent bond between the Au(I) complex and the biomolecule.
18567881 Etanercept treatment in myasthenia gravis. 2008 Etanercept is a tumor necrosis factor (TNF) blocking agent that has been shown to suppress ongoing experimental autoimmune myasthenia gravis (EAMG). This subcutaneously administered TNF blocking agent has also been shown to be safe and effective in several rheumatological diseases including rheumatoid arthritis, psoriasis, and ankylosing spondylitis. A prospective clinical pilot trial of etanercept in corticosteroid-dependent autoimmune myasthenia gravis (MG) patients supports further study into etanercept as a treatment for MG.
18466526 Case-control studies with affected sibships. 2007 Related cases may be included in case-control association studies if correlations between related individuals due to identity-by-descent (IBD) sharing are taken into account. We derived a framework to test for association in a case-control design including affected sibships and unrelated controls. First, a corrected variance for the allele frequency difference between cases and controls was directly calculated or estimated in two ways on the basis of the fixation index FST and the inbreeding coefficient. Then the correlation-corrected association test including controls and affected sibs was carried out. We applied the three strategies to 20 candidate genes on the Genetic Analysis Workshop 15 rheumatoid arthritis data and to 9187 single-nucleotide polymorphisms of replicate one of the Genetic Analysis Workshop 15 simulated data with knowledge of the "answers". The three strategies used to correct for correlation give only minor differences in the variance estimates and yield an almost correct type I error rate for the association tests. Thus, all strategies considered to correct the variance performed quite well.
18466449 Application of an iterative Bayesian variable selection method in a genome-wide associatio 2007 Genome-wide association studies usually involve several hundred thousand of single-nucleotide polymorphisms (SNPs). Conventional approaches face challenges when there are enormous number of SNPs but a relatively small number of samples and, in some cases, are not feasible. We introduce here an iterative Bayesian variable selection method that provides a unique tool for association studies with a large number of SNPs (p) but a relatively small sample size (n). We applied this method to the simulated case-control sample provided by the Genetic Analysis Workshop 15 and compared its performance with stepwise variable selection method. We demonstrated that the results of iterative Bayesian variable selection applied to when p t n are as comparable as those of stepwise variable selection implemented to when n t p. When n > p, the iterative Bayesian variable selection performs better than stepwise variable selection does.
17320408 The role of the chemokine CXCL12 in osteoclastogenesis. 2007 Apr The chemokine CXCL12 (variously termed stromal-derived factor 1 or B cell-stimulating factor) is a highly conserved chemotactic cytokine belonging to the large family of CXC chemokines. CXCL12 has crucial roles in the formation of multiple organ systems during embryogenesis and in the regulation of bone marrow haematopoiesis and immune function in the postnatal organism. Although considered an important factor in normal bone metabolism, recent studies implicate CXCL12 in the pathogenesis of several diseases involving the skeleton, including rheumatoid arthritis and cancers that metastasize to bone. Recent studies have highlighted an emerging role for CXCL12 in the processes of physiological and pathological bone remodelling.
17309320 Future of tissue engineering in rheumatic diseases. 2007 Mar Chronic inflammation during rheumatoid arthritis and degenerative processes during osteoarthritis eventually result in joint destruction. Anti-inflammatory therapies facilitate the inhibition or delay of progressing joint cartilage and bone loss, but do not regenerate these tissues. Surgical procedures are quite unsatisfactory in long-term evaluation and often lead to endoprothetic joint replacement. Present tissue engineering technologies offer new strategies for the treatment of cartilage and bone defects. Here, beyond implantation of cell suspensions, biomaterials combined with tissue-specific cells or mesenchymal stem cells are clinically applied. This review focuses on state-of-the-art and future in situ mesenchymal stem cell-based tissue engineering approaches for joint repair in patients with rheumatic diseases.
17091604 [Chronic autoimmune thyroiditis and connective tissue system diseases]. 2006 Sep Autoimmune thyroiditis is often related to non-specific autoimmune organ diseases such as Rheumatoid Arthritis, Sjögren's syndrome, systemic sclerosis, Systemic Lupus Erythematosus or polymyalgia rheumatica. Etiology of autoimmune diseases has not been clearly discovered yet. In many aspects, mechanisms leading to organ-specific autoimmune diseases are identic with mechanisms causing organ-nonspecific autoimmune disease. In many cases genetic disposal combined with specific antigens can be seen. Another possible factor in terms of endogenesis is genus. External factors are important too, such as undergoing infection, stress situations, exposion to ultraviolet radiation. Authors of this work summarize facts about chronic autoimmune thyroiditis and system connective tissue disease. The most literature supports more frequent appearance of these diseases, while the thyroiditis can appear both in clinical form with typical symptoms and in subclinical form.
17017998 The chemokine receptor CXCR4 as a therapeutic target for several diseases. 2006 Sep CXCR4 is the receptor for a chemokine, CXCL12 (stromal cell-derived factor-1, SDF-1). The CXCL12-CXCR4 axis has been proven to be involved in several problematic diseases, including AIDS, cancer cell metastasis, leukemia cell progression and rheumatoid arthritis (RA). Thus, CXCR4 is thought to be an important therapeutic target to overcome the above diseases. We have developed several specific CXCR4 antagonists.
16925083 Remarkable reduction or disappearance of retroodontoid pseudotumors after occipitocervical 2006 Aug Retroodontoid or periodontoid pseudotumor unassociated with rheumatoid arthritis or hemodialysis is clinically rare. The authors report three cases of retroodontoid pseudotumor that they treated surgically. All patients exhibited myelopathy of the upper cervical spinal cord. Plain radiography depicted atlantoaxial instability in two of the three patients. Spinal cord compression caused by a mass lesion in all patients was clearly demonstrated on magnetic resonance images. In two patients, the mass lesion was not limited to the retroodontoid region and expanded continuously to the cranial base. Posterior laminectomy of the atlas and occipitocervical fusion were performed. After surgery, the pseudotumor disappeared in two cases and was clearly reduced in one case, and neurological symptoms also improved. Retroodontoid pseudotumor is a lesion for which symptomatic improvement can be expected with posterior decompression and fusion, even without direct tumor excision.
16724539 Preparation of a radionuclide/gel formulation for localised radiotherapy to a wide range o 2006 May Localised radiotherapy by instillation of radiolabeled particles is being used to treat rheumatoid arthritis and certain tumors. Such therapy is limited to organs and tissues capable of retaining the radioactive compound until the radioactivity is sufficiently low, and the leakage to other parts of the body is no longer unacceptable. In this study, radiolabeled particles, i.e. 90Y-silica colloid particles, were encapsulated in calcium alginate gels, and the leakage of radioactivity from the gels was monitored. The purpose of the study was to develop a formulation suitable for the localised delivery of radiation therapy to a wide range of organs and tissues. An injectable gel formulation was developed, liberating only small amounts of radioactivity into the surrounding medium. The formulation is a viscous liquid at room temperature and forms a gel on heating to normal body temperature. Thus, it should be suitable for the localised delivery of radiolabeled particles to a wide range of organs and tissues. The study also includes a formulation exhibiting time-dependent gelation. However, this formulation was not found to be suitable for the purpose.
16580976 Cell-surface and cytokine biomarkers in autoimmune and inflammatory diseases. 2006 Apr Increasing emphasis is being placed on biomarkers as indicators of disease states in patients with autoimmune and inflammatory disorders, such as rheumatoid arthritis, multiple sclerosis and systemic lupus erythematosus. Careful description of the expression of cell-surface markers and cytokines produced by T and B lymphocytes can lead to a more complete characterization of disease activity in patient populations, and serve as an indicator of the patient's response to therapy.